title: TLR stimulation of bone marrow lymphoid precursors from childhood acute leukemia modifies their differentiation potentials.
abstract: Acute leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs) in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia.
authors.affiliation: Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, Mexico ; Federico Gómez Children's Hospital, 06720 Mexico City, Mexico ; Medical Sciences Program, National Autonomous University of Mexico, 04510 Mexico City, Mexico.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dorantes-Acosta
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vadillo
authors.forename: Adriana
authors.initials: A
authors.lastname: Contreras-Quiroz
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Balandrán
authors.forename: Lourdes
authors.initials: L
authors.lastname: Arriaga-Pizano
authors.forename: Jessica
authors.initials: J
authors.lastname: Purizaca
authors.forename: Sara
authors.initials: S
authors.lastname: Huerta-Yepez
authors.forename: Elva
authors.initials: E
authors.lastname: Jiménez
authors.forename: Wendy
authors.initials: W
authors.lastname: Aguilera
authors.forename: Aurora
authors.initials: A
authors.lastname: Medina-Sanson
authors.forename: Héctor
authors.initials: H
authors.lastname: Mayani
authors.forename: Rosana
authors.initials: R
authors.lastname: Pelayo
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D018920:Coculture Techniques; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D054503:Lymphoid Progenitor Cells / Q000378:metabolism; D051379:Mice; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000096:biosynthesis*
chemical_list: D051193:Toll-Like Receptors